Unpicking frontotemporal lobar degeneration

Abstract

Not so long ago, frontotemporal lobar degeneration (FTLD) seemed quite simple. Apart from rare variants of Alzheimer's disease and the occasional obscure neurodegenerative disease that could not be classified, FTLD was synonymous with Pick's disease, first described by Arnold Pick (1892) in a series of patients with ‘circumscribed atrophy’ and aphasia. The neuropathological findings in two such patients were later reported by Alois Alzheimer (1911) to include distinct argyrophilic ‘globes’ (subsequently called Pick bodies) within some neurons, and other neurons that were swollen by homogeneously argyrophilic material (Pick cells). Patients whose brains were found to contain the argyrophilic inclusions and swollen neurons were said to have typical Pick's disease. Those who had frontotemporal atrophy in the absence of these features or any alternative diagnosis such as Alzheimer's disease were said to have ‘atypical’ Pick's disease (sometimes subdivided into two or more subgroups, depending largely on the precise distribution of pathology), on the assumption that the underlying pathological process was similar even if the neurons lacked argyrophilic inclusions. In 1986, Pollock et al . (1986) showed that Pick bodies contain the microtubule-associated protein tau and in 1988 they were reported to contain ubiquitin (Love et al. , 1988). Later, the Pick body-like inclusions in several other forms of FTLD were shown also to contain ubiquitin but not tau (Cooper et al. , 1995; Bergmann et al. , 1996). We have come a long way in a relatively short period. Current classifications recognize at least 16 pathological subtypes of FTLD (Mackenzie et al. , 2010). The most recently described category of FTLD is characterized pathologically by aberrant accumulation of …